Since penem antibiotics represented by thienamycin have a broad antibacterial spectrum, they are being watched with keen interest as medicines.
Various processes for producing penem antibiotics have been proposed in, for example, Kametani, Heterocycles, 17, pp. 463-506 (1982) and Shibuya, Yuki Gosei Kauaku, 41, p. 62 (1983). Of these, the processes in which the desired antibiotics are synthesized via 4-acetoxyazetidinone derivatives represented by formula (I) as intermediates are advantageous in that various penem antibiotics can be produced because compounds (I) can react with a variety of nucleophilic agents.
Conventionally known methods for producing 4-acetoxy-azetidinone derivatives (I) include oxidation of a 4-carboxy-azetidinone with lead tetraacetate [Tetrahedron Letters, 23, p. 2293 (1982)], electrolytic oxidation of a 4-carboxyazetidinone [Tetrahedron Letters, 29, p. 1409 (1988)], oxidation of a 4-acetylazetidinone with m-chloroperbenzoic acid (JP-A-61-50964) (the term "JP-A" as used herein means an "unexamined published Japanese patent application"}, and treatment of a 4-silyloxy-azetidinone derivative with acetic anhydride (European Patent 247,378).
In the above methods, in order to introduce an acetoxy group at the 4-position of the azetidinone, an azetidinone derivative having a specific substituent group at the 4-position thereof should first be synthesized, and an acetoxy group should be then introduced by converting this substituent group. However, these methods are defective in that not only the production of such an azetidinone derivative having a specific substituent group at the 4-position thereof is troublesome, but the conversion of the substituent group at the 4-position into an acetoxy group is difficult. For these reasons, the above methods have been unavoidably disadvantageous as an industrial method.
As an expedient for eliminating the above-described drawbacks, it has been proposed to introduce an acetoxy group into an azetidinone at the 4-position thereof by use of a ruthenium compound (JP-A-2-231471). However, in industrialization of this method, further improvements in catalytic activity have been desired.